Serotonin is a nurotransmitter which is widely distributed in human and has a remarkable variety of physiological effects. It is hitherto known that a serotonin receptor includes three subtypes of serotonin 1 receptor, serotonin 2 receptor and serotonin 3 receptor. In addition to these receptors, it is reported by Dumuis, A., et al., Molecular Pharmacology, 34, 880, 1988 that serotonin 4 receptor is existent.
Serotonin 4 receptor is considered to take a part in contraction of the ileum or ascending colon of guinea pig or relaxation of rat esophagus. Cisapride and renzapride, which are stimulants of serotonin 4 receptor, accelerate gastrointestinal motor functions and improve gastrointestinal conditions such as chronic gastritis, heartburn accompanied by postoperative gastroparesis, anorexia, bowel pain, abdominal distension, etc., and are thus considered to be effective for the treatment of gastro-esophagal reflux, intestinal pseudo-obstruction and constipation [Alimentary Pharmacology and Therapeutics, 6, 273, 1992].
As heterocyclic compounds having an activity of antagonizing or stimulating serotonin receptors, European Patent No. 0458636A1 discloses quinolone derivatives which exert on a serotonin 3 receptor antagonizing activity.
On the other hand, U.S. Pat. No. 5,106,851 discloses quinazoline-carboxylic acid derivatives as heterocyclic compounds effective for the treatment of gastrointestinal disorders. However, the compounds are merely known to show an affinity to muscarinic receptors but remain unknown about any action of serotonin receptors.
As stated above, no research has been reported on any heterocyclic compound having an excellent antagonizing or stimulating activity particularly on serotonin 4 receptor.
Accordingly, the .object of the present invention is to provide a novel heterocyclic compound having a potent stimulating activity especially on serotonin 4 receptor and a pharmaceutical use thereof.